During embryogenesis, the developmental potential of individual cells is continuously restricted. During CNS development, neurogenesis largely precedes gliogenesis. Isolated stem cells from the embryonic mouse cerebral cortex, for example, exhibit a distinct order of cell-type production: neuroblasts first and glioblasts later. This is accompanied by changes in their capacity to make neurons versus glia. Thus, multipotent stem cells alter their properties over time and undergo distinct phases of development that play a key role in scheduling production of diverse CNS cells.
Current methods of culturing neural stem cells result in poor self-renewal and limited neuron production, particularly projection neurons. What is needed is a culture system that could provide an almost unlimited source of neural stem cells having a specific developmental capacity for cell-replacement strategies.
Stem cell expansion and differentiation are regulated in vivo by environmental factors encountered in the stem cell niche (1). In the adult, neural stem cells lie close to blood vessels: in the hippocampus (2), the subventricular zone (SVZ) (3), and the songbird higher vocal center (4). In the developing central nervous system (CNS), ventricular zone cells produce vascular endothelial growth factor (VEGF), which attracts vessel growth towards them (5). Thus, vascular cells are close to CNS germinal zones throughout life, and it has been suggested that they form a niche for neural stem cells (2).